HIV drug boosts effects of malaria drug

Researchers in Uganda have found that an anti-retroviral drug used to treat HIV boosts the preventive effects of one specific antimalarial medication.

Drugs are currently not widely used in malaria prevention, with preventive efforts traditionally focused around mosquito nets and insecticides.

Researchers from Uganda's Makerere University College of Health Sciences and the University of California set out to investigate the effects that protease inhibitors, a class of anti-HIV drugs, have on the malaria parasite, which is carried by mosquitoes.

In a trial in Tororo carried out among 170 Ugandan children under five, one group of children was given an anti-HIV drug combination containing protease inhibitors, while the other group was given an anti-HIV cocktail that did not.

Led by Diane Havlir and Moses Kamya, the researchers turned up a surprising result; that one protease inhibitor did indeed reduce the number of malaria cases in the group of children which took it, but not in the way they had imagined.

The protease inhibitor worked by boosting the effectiveness of lumefantrine, a malaria drug in common use, they reported to the 19th Conference on Retroviruses and Opportunistic Infections.

The Tororo trial group that took the protease inhibitors saw a drop in the number of malaria infections of 41%, compared with the control group.

But the researchers concluded that the direct effect of the protease inhibitors was only "modest", compared with the effect of the interaction between protease inhibitor ritonavir and lumefantrine.

Paula Brentlinger of the University of Washington in Seattle said the reductions in malaria episodes reported by the research teams was statistically and clinically significant.

She said the results were particularly heartening, because they had been discovered among one of the most malaria-vulnerable populations in the world.

The researchers realised the link between ritonavir and lumefantrine by identifying the children into those who had taken lumefantrine because of a first malaria episode. In that group, recurrent malaria bouts were dramatically reduced, by as much as 59%.

Lumefantrine is known to remain within the body for several weeks, and researchers speculated that the ritonavir may have limited the liver's ability to remove it from the system, thereby extending its protective effects.

Seattle-based Carlos Campbell of the non-profit group PATH, said that persistent malaria infections were linked to anaemia in many African children, and so the antiretroviral combination might reduce it.

He said that in areas where there is a lot of malaria, it might also influence the choice of antiretroviral drug regimen.

US officials welcomed the findings. S. Patrick Kachur, head of the malaria branch at the US Centers for Disease Control and Prevention (CDC), said it was important to know if ritonavir "potentiates the long tail of lumefantrine".